Gut anaerobes protect against pathogen invasion: Intestinal infections are a common problem for young animals. One explanation is that the protective gut microbiota is not fully established in infants. How the microbiota might protect against pathogens is unclear. Kim et al. found that members of the group of strictly anaerobic, spore-forming bacteria known as clostridia protect neonatal mice against diarrhea-causing pathogens. The protective effect is enhanced by giving mice the metabolite succinate in drinking water. Succinate favors colonization of the neonatal gut by cluster IV and XIVa clostridia and concomitantly excludes Salmonella typhimurium. Science , this issue p. 315

Gut microbiota act beyond the gastrointestinal tract to regulate the physiology of the host. However, their contribution to the antioxidant capacity of the host remains largely understudied. In this study, we observe that gut bacteria increase the steady-state plasma levels of high-antioxidant molecules, reactive sulfur species (RSS), such as hydrogen sulfide and cysteine persulfide (CysSSH), in the host. Moreover, gut bacteria utilize cystine as a substrate to enzymatically produce CysSSH. Administration of cystine to mice increases their plasma levels of RSS and suppresses the concanavalin-A-induced oxidative stress and liver damage in a gut-microbiota-dependent manner. We find that gut bacteria belonging to the Lachnospiraceae and Ruminococcaceae families have a high capacity to produce RSS, requiring pyridoxal 5'-phosphate for their enzymatic reactions. Collectively, our data demonstrate that gut microbiota enhance the antioxidant capacity of the host through the generation of RSS.

Microbiota-accessible carbohydrates (MACs) exert health-promoting effects, but how each MAC impacts gut microbiota and regulates host physiology remains unclear. Here, we show that l-arabinose and sucrose cooperatively act on gut microbiota and exert anti-obesogenic effects. Specifically, l-arabinose, a monosaccharide that is poorly absorbed in the gut and inhibits intestinal sucrase, suppresses diet-induced obesity in mice in the presence of sucrose. Additionally, the suppressive effect of l-arabinose on adiposity is abrogated in mice lacking the short-chain fatty acid (SCFA) receptors GPR43 and GPR41. Mechanistically, l-arabinose increases the relative abundance of acetate and propionate producers (e.g., Bacteroides), while sucrose enhances SCFA production. Furthermore, l-arabinose and sucrose activate the glycolytic and pentose phosphate pathways of Bacteroides, respectively, indicating that they synergistically promote acetate production through distinct pathways. These findings suggest that each MAC has a unique property and thus may serve as a precision gut-microbiota modulator to promote host homeostasis.

_D-Amino acids (_D-AAs) have various functions in mammals and microbes. _D-AAs are produced by gut microbiota and can act as potent bactericidal molecules. Thus, _D-AAs regulate the ecological niche of the intestine; however, the actual impacts of _D-AAs in the gut remain unknown. In this study, we show that _D-Tryptophan (_D-Trp) inhibits the growth of enteric pathogen and colitogenic pathobionts. The growth of Citrobacter rodentium in vitro is strongly inhibited by _D-Trp treatment. Moreover, _D-Trp protects mice from lethal C. rodentium infection via reduction of the pathogen. Additionally, _D-Trp prevents the development of experimental colitis by the depletion of specific microbes in the intestine. _D-Trp increases the intracellular level of indole acrylic acid (IA), a key molecule that determines the susceptibility of enteric microbes to _D-Trp. Treatment with IA improves the survival of mice infected with C. rodentium. Hence, _D-Trp could act as a gut environmental modulator that regulates intestinal homeostasis.

While poorly-absorbed sugar alcohols such as sorbitol are widely used as sweeteners, they may induce diarrhea in some individuals. However, the factors which determine an individual’s susceptibility to sugar alcohol-induced diarrhea remain unknown. Here, we show that specific gut bacteria are involved in the suppression of sorbitol-induced diarrhea. Based on 16S rDNA analysis, the abundance of Enterobacteriaceae bacteria increased in response to sorbitol consumption. We found that Escherichia coli of the family Enterobacteriaceae degraded sorbitol and suppressed sorbitol-induced diarrhea. Finally, we showed that the metabolism of sorbitol by the E. coli sugar phosphotransferase system helped suppress sorbitol-induced diarrhea. Therefore, gut microbiota prevented sugar alcohol-induced diarrhea by degrading sorbitol in the gut. The identification of the gut bacteria which respond to and degrade sugar alcohols in the intestine has implications for microbiome science, processed food science, and public health.

Metabolic syndrome (MetS) is a multifactorial chronic metabolic disorder that affects approximately one billion people worldwide. Recent studies have evaluated whether targeting the gut microbiota can prevent MetS. This study aimed to assess the ability of dietary fiber to control MetS by modulating gut microbiota composition. Sodium alginate (SA) is a seaweed-derived dietary fiber that suppresses high-fat diet (HFD)-induced MetS via an effect on the gut microbiota. We observed that SA supplementation significantly decreased body weight gain, cholesterol levels, and fat weight, while improving glucose tolerance in HFD-fed mice. SA changed the gut microbiota composition and significantly increased the abundance of Bacteroides. Antibiotic treatment completely abolished the suppressive effects of SA on MetS. Mechanistically, SA decreased the number of colonic inflammatory monocytes, which promote MetS development, in a gut microbiota-dependent manner. The abundance of Bacteroides was negatively correlated with that of inflammatory monocytes and positively correlated with the levels of several gut metabolites. The present study revealed a novel food function of SA in preventing HFD-induced MetS through its action on gut microbiota.